A Cyclin-dependent Kinase Inhibitor (p21(WAF1/CIP1)) Affects Thymidine Incorporation in Human Liver Cancer Cells

Overview

Journal Br J Cancer

Specialty Oncology

Date 2002 Mar 1

PMID 11870547

Citations 4

Authors

Y Gong

S Deng

M Zhang

G Wang

G Y Minuk

F Burczynski

Affiliations

Soon will be listed here.

Abstract

p21(WAF1/CIP1) is a universal cyclin-dependent kinase inhibitor. To investigate the role of p21(WAF1/CIP1) in proliferation of human liver cancer cells, we examined the expression of p53, p21(WAF1/CIP1), cdk2 and cdk4 expression in two human liver cancer cell lines (HepG2 and PLC/PRF/5 cells). The effects of p21(WAF1/CIP1) on [(3)H]thymidine incorporation and cdks were also examined in these cells. HepG2 cells expressed all these proteins with lower level of cdk4. PLC/PRF/5 cells expressed the other proteins except p21(WAF1/CIP1). Transfection of p21(WAF1/CIP1) gene inhibited [(3)H]thymidine incorporation of both cells with different extent. Although the transfection of p21(WAF1/CIP1) did not affect cdk2 and cdk4 expression, it did reduce cdk2 kinase activity by 20%. These results suggest that: (a) p21(WAF1/CIP1) involved in DNA synthesis of human liver cancer cells; (b) p21(WAF1/CIP1) could be a target gene for the treatment of human hepatocellular carcinoma.

Citing Articles

Human amniotic membrane conditioned medium inhibits proliferation and modulates related microRNAs expression in hepatocarcinoma cells.

Riedel R, Perez-Perez A, Carmona-Fernandez A, Jaime M, Casale R, Duenas J Sci Rep. 2019; 9(1):14193.

PMID: 31578445 PMC: 6775050. DOI: 10.1038/s41598-019-50648-5.

Berberine regulates the protein expression of multiple tumorigenesis-related genes in hepatocellular carcinoma cell lines.

Chuang T, Wu H, Min J, Diamond M, Azziz R, Chen Y Cancer Cell Int. 2017; 17:59.

PMID: 28572744 PMC: 5450260. DOI: 10.1186/s12935-017-0429-3.

Function of oval cells in hepatocellular carcinoma in rats.

Fang C, Gong J, Zhang W World J Gastroenterol. 2004; 10(17):2482-7.

PMID: 15300889 PMC: 4572146. DOI: 10.3748/wjg.v10.i17.2482.

Aberrant promoter methylation profiles of tumor suppressor genes in hepatocellular carcinoma.

Yang B, Guo M, Herman J, Clark D Am J Pathol. 2003; 163(3):1101-7.

PMID: 12937151 PMC: 1868243. DOI: 10.1016/S0002-9440(10)63469-4.

References

Hui A, Kanai Y, Sakamoto M, Tsuda H, Hirohashi S . Reduced p21(WAF1/CIP1) expression and p53 mutation in hepatocellular carcinomas. Hepatology. 1997; 25(3):575-9. DOI: 10.1002/hep.510250314. View

Warbrick E, Lane D, Glover D, Cox L . A small peptide inhibitor of DNA replication defines the site of interaction between the cyclin-dependent kinase inhibitor p21WAF1 and proliferating cell nuclear antigen. Curr Biol. 1995; 5(3):275-82. DOI: 10.1016/s0960-9822(95)00058-3. View

Naka T, Toyota N, Kaneko T, Kaibara N . Protein expression of p53, p21WAF1, and Rb as prognostic indicators in patients with surgically treated hepatocellular carcinoma. Anticancer Res. 1998; 18(1B):555-64. View

Qin L, Ng I, Fan S, Ng M . p21/WAF1, p53 and PCNA expression and p53 mutation status in hepatocellular carcinoma. Int J Cancer. 1998; 79(4):424-8. DOI: 10.1002/(sici)1097-0215(19980821)79:4<424::aid-ijc19>3.0.co;2-4. View

Shima N, Stolz D, Miyazaki M, Gohda E, Higashio K, Michalopoulos G . Possible involvement of p21/waf1 in the growth inhibition of HepG2 cells induced by hepatocyte growth factor. J Cell Physiol. 1998; 177(1):130-6. DOI: 10.1002/(SICI)1097-4652(199810)177:1<130::AID-JCP14>3.0.CO;2-H. View

Shi Y, Hui A, Takayama T, Li X, Cui X, Makuuchi M . Reduced p21(WAF1/CIP1) protein expression is predominantly related to altered p53 in hepatocellular carcinomas. Br J Cancer. 2000; 83(1):50-5. PMC: 2374549. DOI: 10.1054/bjoc.2000.1310. View

Aviv H, Leder P . Purification of biologically active globin messenger RNA by chromatography on oligothymidylic acid-cellulose. Proc Natl Acad Sci U S A. 1972; 69(6):1408-12. PMC: 426713. DOI: 10.1073/pnas.69.6.1408. View

Aden D, FOGEL A, Plotkin S, Damjanov I, Knowles B . Controlled synthesis of HBsAg in a differentiated human liver carcinoma-derived cell line. Nature. 1979; 282(5739):615-6. DOI: 10.1038/282615a0. View

Koch S, Freytag von Loringhoven A, Kahmann R, Hofschneider P, Koshy R . The genetic organization of integrated hepatitis B virus DNA in the human hepatoma cell line PLC/PRF/5. Nucleic Acids Res. 1984; 12(17):6871-86. PMC: 320123. DOI: 10.1093/nar/12.17.6871. View

10.

Hosono S, Lee C, Chou M, Yang C, Shih C . Molecular analysis of the p53 alleles in primary hepatocellular carcinomas and cell lines. Oncogene. 1991; 6(2):237-43. View

11.

Gong Y, Anzai Y, Murphy L, Ballejo G, Holinka C, GURPIDE E . Transforming growth factor gene expression in human endometrial adenocarcinoma cells: regulation by progestins. Cancer Res. 1991; 51(20):5476-81. View

12.

Xiong Y, Zhang H, Beach D . D type cyclins associate with multiple protein kinases and the DNA replication and repair factor PCNA. Cell. 1992; 71(3):505-14. DOI: 10.1016/0092-8674(92)90518-h. View

13.

Hsu I, Tokiwa T, Bennett W, Metcalf R, Welsh J, Sun T . p53 gene mutation and integrated hepatitis B viral DNA sequences in human liver cancer cell lines. Carcinogenesis. 1993; 14(5):987-92. DOI: 10.1093/carcin/14.5.987. View

14.

El-Deiry W, Tokino T, Velculescu V, Levy D, Parsons R, Trent J . WAF1, a potential mediator of p53 tumor suppression. Cell. 1993; 75(4):817-25. DOI: 10.1016/0092-8674(93)90500-p. View

15.

Xiong Y, Hannon G, Zhang H, Casso D, Kobayashi R, Beach D . p21 is a universal inhibitor of cyclin kinases. Nature. 1993; 366(6456):701-4. DOI: 10.1038/366701a0. View

16.

El-Deiry W, Harper J, OConnor P, Velculescu V, Canman C, Jackman J . WAF1/CIP1 is induced in p53-mediated G1 arrest and apoptosis. Cancer Res. 1994; 54(5):1169-74. View

17.

Noda A, Ning Y, Venable S, Smith J . Cloning of senescent cell-derived inhibitors of DNA synthesis using an expression screen. Exp Cell Res. 1994; 211(1):90-8. DOI: 10.1006/excr.1994.1063. View

18.

Waga S, Hannon G, Beach D, Stillman B . The p21 inhibitor of cyclin-dependent kinases controls DNA replication by interaction with PCNA. Nature. 1994; 369(6481):574-8. DOI: 10.1038/369574a0. View

19.

Flores-Rozas H, Kelman Z, Dean F, Pan Z, Harper J, Elledge S . Cdk-interacting protein 1 directly binds with proliferating cell nuclear antigen and inhibits DNA replication catalyzed by the DNA polymerase delta holoenzyme. Proc Natl Acad Sci U S A. 1994; 91(18):8655-9. PMC: 44665. DOI: 10.1073/pnas.91.18.8655. View

20.

Hunter T, Pines J . Cyclins and cancer. II: Cyclin D and CDK inhibitors come of age. Cell. 1994; 79(4):573-82. DOI: 10.1016/0092-8674(94)90543-6. View